Narasimhulu Chandrakala Aluganti, Singla Dinender K
Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA.
Antioxidants (Basel). 2023 Jan 31;12(2):331. doi: 10.3390/antiox12020331.
Diabetic myopathy involves hyperglycemia, oxidative stress, and inflammation. However, the role of hypercholesterolemia-induced inflammation-mediated pathological mechanisms leading to fibrosis, sarcopenia, deterioration of muscle, and muscle dysfunction in diabetes is not well understood. In this study, we investigated the novel role of bone morphogenetic protein-7 (BMP-7) in ameliorating metabolic alterations, inflammation, pyroptosis, TGF-β/SMAD cell signaling mechanisms, and progression of diabetic myopathy. C57BL/6J mice were treated with saline, streptozotocin (STZ), or STZ+BMP-7. Diabetes was confirmed by increased fasting glucose levels and a glucose tolerance test. Gastrocnemius muscle and blood samples were collected for lipid and tissue analysis using various methods. A significant increase in hyperglycemia resulted in an increase in lipid accumulation, monocyte infiltration, and inflammation, as well as an increase in pyroptotic markers and signaling markers in diabetic muscle myocytes. A structural analysis showed significant muscle loss, and increased muscle deterioration and fibrosis leading to muscle dysfunction. BMP-7 attenuated pathological processes that resulted in significantly improved muscle function. We report, for the first time, that increased hyperlipidemia aggravates inflammation-induced pyroptosis, resulting in significant muscle loss, sarcopenia, and adverse skeletal muscle remodeling in diabetic muscle myopathy. Interventional treatment with BMP-7 attenuates hypercholesterolemia-induced inflammation-mediated sarcopenia and adverse muscle remodeling, suggesting BMP-7 could be a potential treatment option for diabetic muscle myopathy.
糖尿病性肌病涉及高血糖、氧化应激和炎症。然而，高胆固醇血症诱导的炎症介导的病理机制在糖尿病中导致纤维化、肌肉减少症、肌肉退化和肌肉功能障碍的作用尚未得到充分了解。在本研究中，我们研究了骨形态发生蛋白-7（BMP-7）在改善代谢改变、炎症、细胞焦亡、TGF-β/SMAD细胞信号传导机制以及糖尿病性肌病进展方面的新作用。将C57BL/6J小鼠用生理盐水、链脲佐菌素（STZ）或STZ+BMP-7进行处理。通过空腹血糖水平升高和葡萄糖耐量试验确认糖尿病。使用各种方法收集腓肠肌和血液样本进行脂质和组织分析。高血糖显著增加导致糖尿病肌肉肌细胞中脂质积累、单核细胞浸润和炎症增加，以及细胞焦亡标志物和信号标志物增加。结构分析显示肌肉明显丢失，肌肉退化和纤维化增加，导致肌肉功能障碍。BMP-7减轻了病理过程，从而显著改善了肌肉功能。我们首次报告，高脂血症增加会加重炎症诱导的细胞焦亡，导致糖尿病肌肉肌病中明显的肌肉丢失、肌肉减少症和不良的骨骼肌重塑。用BMP-7进行干预治疗可减轻高胆固醇血症诱导的炎症介导的肌肉减少症和不良的肌肉重塑，表明BMP-7可能是糖尿病肌肉肌病的一种潜在治疗选择。
